Distinct peripheral blood RNA responses to Salmonella in pigs differing in Salmonella shedding levels: Intersection of IFNG, TLR and miRNA pathways

Ting Hua Huang, Jolita J. Uthe, Shawn M.D. Bearson, Cumhur Yusuf Demirkale, Dan Nettleton, Susan Knetter, Curtis Christian, Amanda E. Ramer-Tait, Michael J. Wannemuehler, Christopher K. Tuggle

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Transcriptomic analysis of the response to bacterial pathogens has been reported for several species, yet few studies have investigated the transcriptional differences in whole blood in subjects that differ in their disease response phenotypes. Salmonella species infect many vertebrate species, and pigs colonized with Salmonella enterica serovar Typhimurium (ST) are usually asymptomatic, making detection of these Salmonella-carrier pigs difficult. The variable fecal shedding of Salmonella is an important cause of foodborne illness and zoonotic disease. To investigate gene pathways and biomarkers associated with the variance in Salmonella shedding following experimental inoculation, we initiated the first analysis of the whole blood transcriptional response induced by Salmonella. A population of pigs (n = 40) was inoculated with ST and peripheral blood and fecal Salmonella counts were collected between 2 and 20 days post-inoculation (dpi). Two groups of pigs with either low shedding (LS) or persistent shedding (PS) phenotypes were identified. Global transcriptional changes in response to ST inoculation were identified by Affymetrix Genechip® analysis of peripheral blood RNA at day 0 and 2 dpi. ST inoculation triggered substantial gene expression changes in the pigs and there was differential expression of many genes between LS and PS pigs. Analysis of the differential profiles of gene expression within and between PS and LS phenotypic classes identified distinct regulatory pathways mediated by IFN-γ, TNF, NF-κB, or one of several miRNAs. We confirmed the activation of two regulatory factors, SPI1 and CEBPB, and demonstrated that expression of miR-155 was decreased specifically in the PS animals. These data provide insight into specific pathways associated with extremes in Salmonella fecal shedding that can be targeted for further exploration on why some animals develop a carrier state. This knowledge can also be used to develop rational manipulations of genetics, pharmaceuticals, nutrition or husbandry methods to decrease Salmonella colonization, shedding and spread.

Original languageEnglish (US)
Article numbere28768
JournalPloS one
Volume6
Issue number12
DOIs
StatePublished - Dec 14 2011

Fingerprint

Salmonella
MicroRNAs
microRNA
Blood
Swine
RNA
swine
blood
serotypes
Foodborne Diseases
Gene expression
Animals
Genes
Phenotype
Gene Expression
carrier state
phenotype
Carrier State
gene expression
Salmonella enterica

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Huang, T. H., Uthe, J. J., Bearson, S. M. D., Demirkale, C. Y., Nettleton, D., Knetter, S., ... Tuggle, C. K. (2011). Distinct peripheral blood RNA responses to Salmonella in pigs differing in Salmonella shedding levels: Intersection of IFNG, TLR and miRNA pathways. PloS one, 6(12), [e28768]. https://doi.org/10.1371/journal.pone.0028768

Distinct peripheral blood RNA responses to Salmonella in pigs differing in Salmonella shedding levels : Intersection of IFNG, TLR and miRNA pathways. / Huang, Ting Hua; Uthe, Jolita J.; Bearson, Shawn M.D.; Demirkale, Cumhur Yusuf; Nettleton, Dan; Knetter, Susan; Christian, Curtis; Ramer-Tait, Amanda E.; Wannemuehler, Michael J.; Tuggle, Christopher K.

In: PloS one, Vol. 6, No. 12, e28768, 14.12.2011.

Research output: Contribution to journalArticle

Huang, TH, Uthe, JJ, Bearson, SMD, Demirkale, CY, Nettleton, D, Knetter, S, Christian, C, Ramer-Tait, AE, Wannemuehler, MJ & Tuggle, CK 2011, 'Distinct peripheral blood RNA responses to Salmonella in pigs differing in Salmonella shedding levels: Intersection of IFNG, TLR and miRNA pathways', PloS one, vol. 6, no. 12, e28768. https://doi.org/10.1371/journal.pone.0028768
Huang, Ting Hua ; Uthe, Jolita J. ; Bearson, Shawn M.D. ; Demirkale, Cumhur Yusuf ; Nettleton, Dan ; Knetter, Susan ; Christian, Curtis ; Ramer-Tait, Amanda E. ; Wannemuehler, Michael J. ; Tuggle, Christopher K. / Distinct peripheral blood RNA responses to Salmonella in pigs differing in Salmonella shedding levels : Intersection of IFNG, TLR and miRNA pathways. In: PloS one. 2011 ; Vol. 6, No. 12.
@article{69c7d4be92e94342b0b5424819db8137,
title = "Distinct peripheral blood RNA responses to Salmonella in pigs differing in Salmonella shedding levels: Intersection of IFNG, TLR and miRNA pathways",
abstract = "Transcriptomic analysis of the response to bacterial pathogens has been reported for several species, yet few studies have investigated the transcriptional differences in whole blood in subjects that differ in their disease response phenotypes. Salmonella species infect many vertebrate species, and pigs colonized with Salmonella enterica serovar Typhimurium (ST) are usually asymptomatic, making detection of these Salmonella-carrier pigs difficult. The variable fecal shedding of Salmonella is an important cause of foodborne illness and zoonotic disease. To investigate gene pathways and biomarkers associated with the variance in Salmonella shedding following experimental inoculation, we initiated the first analysis of the whole blood transcriptional response induced by Salmonella. A population of pigs (n = 40) was inoculated with ST and peripheral blood and fecal Salmonella counts were collected between 2 and 20 days post-inoculation (dpi). Two groups of pigs with either low shedding (LS) or persistent shedding (PS) phenotypes were identified. Global transcriptional changes in response to ST inoculation were identified by Affymetrix Genechip{\circledR} analysis of peripheral blood RNA at day 0 and 2 dpi. ST inoculation triggered substantial gene expression changes in the pigs and there was differential expression of many genes between LS and PS pigs. Analysis of the differential profiles of gene expression within and between PS and LS phenotypic classes identified distinct regulatory pathways mediated by IFN-γ, TNF, NF-κB, or one of several miRNAs. We confirmed the activation of two regulatory factors, SPI1 and CEBPB, and demonstrated that expression of miR-155 was decreased specifically in the PS animals. These data provide insight into specific pathways associated with extremes in Salmonella fecal shedding that can be targeted for further exploration on why some animals develop a carrier state. This knowledge can also be used to develop rational manipulations of genetics, pharmaceuticals, nutrition or husbandry methods to decrease Salmonella colonization, shedding and spread.",
author = "Huang, {Ting Hua} and Uthe, {Jolita J.} and Bearson, {Shawn M.D.} and Demirkale, {Cumhur Yusuf} and Dan Nettleton and Susan Knetter and Curtis Christian and Ramer-Tait, {Amanda E.} and Wannemuehler, {Michael J.} and Tuggle, {Christopher K.}",
year = "2011",
month = "12",
day = "14",
doi = "10.1371/journal.pone.0028768",
language = "English (US)",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - Distinct peripheral blood RNA responses to Salmonella in pigs differing in Salmonella shedding levels

T2 - Intersection of IFNG, TLR and miRNA pathways

AU - Huang, Ting Hua

AU - Uthe, Jolita J.

AU - Bearson, Shawn M.D.

AU - Demirkale, Cumhur Yusuf

AU - Nettleton, Dan

AU - Knetter, Susan

AU - Christian, Curtis

AU - Ramer-Tait, Amanda E.

AU - Wannemuehler, Michael J.

AU - Tuggle, Christopher K.

PY - 2011/12/14

Y1 - 2011/12/14

N2 - Transcriptomic analysis of the response to bacterial pathogens has been reported for several species, yet few studies have investigated the transcriptional differences in whole blood in subjects that differ in their disease response phenotypes. Salmonella species infect many vertebrate species, and pigs colonized with Salmonella enterica serovar Typhimurium (ST) are usually asymptomatic, making detection of these Salmonella-carrier pigs difficult. The variable fecal shedding of Salmonella is an important cause of foodborne illness and zoonotic disease. To investigate gene pathways and biomarkers associated with the variance in Salmonella shedding following experimental inoculation, we initiated the first analysis of the whole blood transcriptional response induced by Salmonella. A population of pigs (n = 40) was inoculated with ST and peripheral blood and fecal Salmonella counts were collected between 2 and 20 days post-inoculation (dpi). Two groups of pigs with either low shedding (LS) or persistent shedding (PS) phenotypes were identified. Global transcriptional changes in response to ST inoculation were identified by Affymetrix Genechip® analysis of peripheral blood RNA at day 0 and 2 dpi. ST inoculation triggered substantial gene expression changes in the pigs and there was differential expression of many genes between LS and PS pigs. Analysis of the differential profiles of gene expression within and between PS and LS phenotypic classes identified distinct regulatory pathways mediated by IFN-γ, TNF, NF-κB, or one of several miRNAs. We confirmed the activation of two regulatory factors, SPI1 and CEBPB, and demonstrated that expression of miR-155 was decreased specifically in the PS animals. These data provide insight into specific pathways associated with extremes in Salmonella fecal shedding that can be targeted for further exploration on why some animals develop a carrier state. This knowledge can also be used to develop rational manipulations of genetics, pharmaceuticals, nutrition or husbandry methods to decrease Salmonella colonization, shedding and spread.

AB - Transcriptomic analysis of the response to bacterial pathogens has been reported for several species, yet few studies have investigated the transcriptional differences in whole blood in subjects that differ in their disease response phenotypes. Salmonella species infect many vertebrate species, and pigs colonized with Salmonella enterica serovar Typhimurium (ST) are usually asymptomatic, making detection of these Salmonella-carrier pigs difficult. The variable fecal shedding of Salmonella is an important cause of foodborne illness and zoonotic disease. To investigate gene pathways and biomarkers associated with the variance in Salmonella shedding following experimental inoculation, we initiated the first analysis of the whole blood transcriptional response induced by Salmonella. A population of pigs (n = 40) was inoculated with ST and peripheral blood and fecal Salmonella counts were collected between 2 and 20 days post-inoculation (dpi). Two groups of pigs with either low shedding (LS) or persistent shedding (PS) phenotypes were identified. Global transcriptional changes in response to ST inoculation were identified by Affymetrix Genechip® analysis of peripheral blood RNA at day 0 and 2 dpi. ST inoculation triggered substantial gene expression changes in the pigs and there was differential expression of many genes between LS and PS pigs. Analysis of the differential profiles of gene expression within and between PS and LS phenotypic classes identified distinct regulatory pathways mediated by IFN-γ, TNF, NF-κB, or one of several miRNAs. We confirmed the activation of two regulatory factors, SPI1 and CEBPB, and demonstrated that expression of miR-155 was decreased specifically in the PS animals. These data provide insight into specific pathways associated with extremes in Salmonella fecal shedding that can be targeted for further exploration on why some animals develop a carrier state. This knowledge can also be used to develop rational manipulations of genetics, pharmaceuticals, nutrition or husbandry methods to decrease Salmonella colonization, shedding and spread.

UR - http://www.scopus.com/inward/record.url?scp=83155167595&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=83155167595&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0028768

DO - 10.1371/journal.pone.0028768

M3 - Article

C2 - 22174891

AN - SCOPUS:83155167595

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e28768

ER -